JAKi cycling following inadequate response to a first JAKi in patients with rheumatoid arthritis (RA) appears to be as effective as switching to treatment with a bDMARD, according to findings of a large international study.

The research also revealed that when the reason for ceasing initial JAKi treatment was an adverse event (AE), it was more likely that the second round of JAKi would also be stopped for side effects.

Findings of the observational study, which involved 17 national JAK-pot registries and 2000 patients who had an inadequate response to or who experienced an AE with a first JAKi, will help guide clinical decision-making after JAKi failure to better inform “in this increasingly frequent scenario”, the authors noted.

In the UK there has perhaps been less experience of JAKi cycling as opposed to switching to bDMARD therapy, but this is slowly changing, according to Professor Philip Conaghan, a Professor of Musculoskeletal Medicine and Honorary Consultant Rheumatologist for Leeds Teaching Hospital NHS Trust.

And while the study’s findings won’t represent a marked change to current therapeutic strategies in the UK, “it’s good to know that either strategy resulted in similar efficacy in this real-world data,” he told the limbic.

“It’s also important to know that stopping a JAKi because of an adverse event increased the risk of an event happening with a subsequent JAKi,” he said, though noted that whether the AE experienced with the second JAKi was of a similar nature to the first remains unclear.

According to the authors, “for this very interesting topic, more granular data, available in specific registers, will be necessary to determine if specific AE recurs with the use of a second JAKi, with this finding suggestive of a class effect”.

Further commenting on the study, Prof Conaghan said it was worth noting that “the majority of first JAKi’s used were not JAK1 selective agents, so it’s not clear from this data if reversing the order (JAK1 selective 1st) would demonstrate similar efficacy”.

Of the 2,000 patients in the trial, 365 were treated with a second JAKi and 1635 switched to a bDMARD. Compared with patients switching to bDMARD, those cycling to another JAKi were older, had longer disease duration, were more often seropositive, received a higher number of previous bDMARDs and had longer exposure to first JAKi treatment, according to the paper, published in The Annals of the Rheumatic Diseases.

The investigators found no link between the type of the first JAKi or the reason for discontinuing it and the subsequent decision to cycle a second JAKi or switch to a bDMARD, nor a significant difference in the proportion of patients stopping the second treatment round due to ineffectiveness. Measures of disease activity were also similar in both cohorts, they noted.

There was also no crude difference in drug retention between switching of cycling after 2 years’ follow-up, though adjusted analysis showed that cycling to another JAKi was linked with higher retention versus the use of a bDMARD (HR for withdrawal 0.82).

The study had several key limitations, including that heterogeneity of data from the different registries could not be assessed, and that the primary outcome of overall drug retention might have been influenced by other factors, such as the number of alternative treatment options available and the characteristics of the patient population.

Nevertheless, it provides “clinically meaningful evidence”, based on ‘real-life’ clinical practice, that could help inform therapeutic strategy for patients with RA after failure to a first JAKi.